This study investigates the potential of soy protein isolate (SPI) to enhance the bioaccessibility of oleic acid (OA), a beneficial fatty acid linked to reduced blood pressure and cardiovascular risk. Using an in vitro digestion model, we examined how the interactions between SPI-derived peptides and bile salts (BS) evolve during gastric and gastroduodenal digestion and how these interactions influence OA micellar solubility. SPI with a soluble fraction (SF) of 16% was digested for 10 and 60 min (tg10 and tg60), and the resulting digesta were evaluated for their ability to enhance OA solubilization in BS micelles. SF increased to 52.3% (tg10) and 64.7% (tg60) and reached 95.8% in the presence of BS under duodenal conditions. Consequently, OA solubilization improved by up to 82% compared to that of BS alone, highlighting the role of soy peptides in promoting lipid bioaccessibility through BS-peptide interactions during digestion.